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underway to evaluate whether longer treatment with methylprednisolone or the use of a different steroid may provide even greater benefit. This year,
NINDS is establishing a pilot program of regional clinical research centers
fo: head and spinal cord injury. These centers will develop improved
therapies, promote research on restoration and preservation of function after injury, and provide the environment necessary for the recruitment and
training of investigators for research on central nervous system trauma. The regional centers will add an important dimension to the NINDS research effort
in 1992 to improve the outcome for many of the estimated 10,000 Americans who
will have a spinal cord injury and the 500,000 who will experience a head
NINDS scientists and grantees are pursuing other avenues to "tease out"
the various chemical and cellular events triggered by injury to the nervous
system and devise methods to block or enhance nerve cell activity for
therapeutic effect. For instance, in stroke patients, damaged nerve cells cán spilt out dangerous levels of excitatory amino acids and produce toxic
supercharged molecules of oxygen known as free radicals, The next step is to
evaluate promising agents to neutralize these chemicals and prevent the
progression of stroke. Research studies are also defining the role of free
radicals in Parkiason's disease and also the damaging interaction between
free radicals and blood vessels in the brain that can result from seizures.
Investigators are pursuing recent evidence that suggests the same mechanism
to secrete excitotoxins may be at work in head injury and neuro-AIDS.
Greater attention can now be given to study of the selective
vulnerability and degeneration of nerve cell populations. ' Oui Institute's
research objective is to prevent brain cell degeneration or arrest it in the very earliest stage of diseases such as Alzheimer's disease and Parkinson's
disease. Aged, nonhuman primates are an important research model for
Alzheimer's disease, helping to elucidate the development of nerve cell
abnormalities and the deposition of amyloid protein in the plaques
characteristic of this disease.
New genetic studies, neurochemical studies,
and the development of advanced imaging methodologies are being emphasized to
shed more light on the fundamental cause of Alzheimer's disease.
tern effects of deprenyl and the value of tocopherol--a component of vitamin
E--in combination with deprenyl to treat people with Parkinson's disease are
being evaluated in an ongoing clinical trial, Study of tissues from people
with amyotrophic lateral sclerosis, or Lou Gehrig's disease, has provided a
lead to evaluate the use of branched-chain amino acids for this disease.
One third of the people who will have a stroke this year will become
permanently disabled: stroke is the most common cause of disability requiring
The NINDS research effort on stroke will be enriched by a
newly established intramural program.
We also have ongoing clinical trials
to evaluate clot-dissolving agents--tPA and heparinoids--for their
effectiveness in limiting brain damage from ischemic stroke.
We are working
with a time-frame of only 90 minutes to three hours to determine whether tPA
must be given as an emergency measure in order to be effective.
also underway to elucidate risk factors and prevent stroke in those people at
risk for an initial insult or recurrence.
Within the past year, the NINDS
found that aspirin and warfarin were so effective in preventing stroke in
people with atrial fibrillation that as many as 30,000 people could be spared
from a stroke this year, at a potential health care savings of $200 million.
Early results from another, ongoing study have related ethnic differences in
risk factors to differences in stroke type and outcome.
NINDS has revised
and reissued a program announcement to encourage new studies in Blacks, other
minorities, and women to improve our understanding of different risk factors
and types of stroke in various populations.
Intramural scientists using magnetic resonance imaging (MRI) have
evidence that multiple sclerosis (MS) progressively attacks the central nervous system even when patients may be relatively symptom-free. This finding will change the way many patients are treated, especially in the
investigators are deciphering the immunologic processes related to MS and
exploring new forms of treatment such as the possibility of a T-cell vaccine.
At a minimum, 25 percent of all genetic disorders affect the brain and
nervous system, some estimate that there are neurological consequences in
70 percent of all genetic disorders. Neurogenetics research is brimming with
à proportional number of research opportunities.
The chromosomal bases for
19 neurological or neuromuscular disorders are now known.
neurofibromatosis I (NF-1) gene has been located on chromosome 17; ongoing research will clarify the gene's normal function and its role in the symptoms
of NF-1 and other disorders of cell growth such as cancer.
closing in on the genetic basis of some forms of epilepsy. Intramural
investigators are refining the optimal dose for enzyme replacement therapy in
Type 1 Caucher's disease while continuing the development of methods to
repair or replace the defective gene.
Dystrophin research has unexpectedly
revealed that other genes may be producing proteins that can "pinch hit" for
linkage studies and studies of cell biochemistry are probing independently
the underlying causes of the various types of Batten's disease.
studies, researchers are working to isolate and sequence the gene for the
animal model of narcolepsy. While investigators continue work to localize
the genetic defect in Huntington's disease (HD), research to determine the
physiologic defect and possible therapies has progressed; preliminary efforts
are underway to test the efficacy of a drug called idebenone to protect at
risk brain cells. Transgenic mice are also being developed as a genetic.
model for HD--an invaluable tool for the expected wave of new studies once
the gene is found.
An estimated 10 to 15 percent of all children have mild cognitive
deficits or learning disabilities. This year, an estimated 9,000 babies will
develop cerebral palsy and several thousand more babies and children will
have to live with--or die from--the neurological consequences of their
mother', drug abuse. An ongoing multidisciplinary study to develop, standardize, and validate a uniform classification system for the diagnosis
of children with higher cortical dysfunctions will facilitate research.
Improved treatments for epilepsy in the pediatric age group are a priority
for the Institute.
As evidenced by the advances and initiatives described here, we cannot
separate progress in prevention, treatment, and diagnosis from the importance
of basic neuroscience research. Neurochemistry and neurobiology are
providing important leads to understand cognition and behavior.
grantees recently found that one possible mechanism for strengthening long
term neural interactions appears to be the ability of the sending cell in
"memory centers" to release more neurotransmitter. Studies of single nerve
cell activity are feeding into better understanding of brain circuits
activated by normal cognitive functions or affected by disease.
Brain imaging technology continues to push
ack the limits of our
ability to study the living brain.
Experiments with positron-emission
tomography (PET) have linked discrete areas of the brain to word-processing
tasks and have confirmed the unique role PET has for understanding the higher
New PET tracer chemicals are opening the door to view
the working circuitry of the brain.
MRI has been established as a critical
tool for research on neuro-AIDS and multiple sclerosis (MS); new studies will
further elaborate understanding of how MS attacks the nervous system and will
be very important in evaluating the effectiveness of treatments.
application of several techniques to the same research problem is proving
very fruitful; PET, MRI, and magnetoencephalography (MEG) provide
complementary information necessary to precisely diagnose and localize the
epileptic focus--especially critical when considering surgery. Ongoing
research seeks to overcome technological barriers to better integrate data from PET and MRI. These exciting opportunities underscore the importance of
brain imaging centers in which these technologies could be integrated and
applied to brain research.
Exciting work with neural prostheses points the way to restoration of
function in the damaged nervous system.
A neural prosthesis that will
utilize extension movement in the wrist to control opening and closing of the
hand is under development.
A brain probe containing both electrodes and
cultured neurons is being developed to make very specific connections with
the central nervous system.
Scientists are also studying genes called into
action after traumatic injury to the nervous system for their potential to
promote nerve cell growth and regeneration.
The declaration of the 1990s as the Decade of the Brain has generated
new enthusiasm among neuroscientists, stimulated international collaborative
research efforts, and provided a focus for efforts to highlight and maintain
the U.S. lead in research, medicine, and biotechnology.
The promise of the
"Decade" has provided in its first year new treatments benefiting many
Americang--treatments which in many cases have the added plus of being
inexpensive or cost-saving. The potential for further progress, as outlined
in the "NINDS Implementation Plan for the Decade of the Brain," impacts
particularly vulnerable segments of our population--elderly, children, and
minorities--and encompasses many of the major health care problems facing the
nation today, such as AIDS and drug abuse. Significant progress has been
achieved in the neurosciences in just the past few years.
We are optimistic
that in the year 2000, when we look back to see what has been accomplished in
the "Decade of the Brain", we will be pleased with the progress made in
understanding the human brain and significantly improving the quality of
Mr. Chairman, the FY 1992 budget request for this Institute is
I am pleased to answer any questions you might have.
BIOGRAPHICAL SKETCH OF DR. MURRAY GOLDSTEIN
October 13, 1925, New York, New York
EDUCATION: B.1., New York University, 1947; D.O., Des Moines still college of Osteopathic Medicine, 1950; M.P.8., University of California, School of Public Health, 1959; Mayo clinic (Neurology), 1968.
PROFESSIONAL BISTORI : Director, NINDS, 1982-present; Acting Director,
PROFESSIONAL ORGANIZATIONS: American Acadeny of Neurology: American
HONORS, AWARDS: Beta Alpha Epsilon, Biology National Bonor Society, NYU; Psi chi, Psychology National Honor Society, NYU; Sigma Alpha, Osteopathic Scholarship National Honor Society, College of Osteopathic Medicine; Delta